Coating-substrate adhesion in cold spray is a paramount property, the mechanisms of which are not yet well elucidated. These mechanisms are governed by metallurgical and morphological phenomena occuring when coldsprayed particles impinge on the substrate. To go into these mechanisms, due to the intrinsic characteristics of the cold spray process, i.e. the low-temperature and high velocity of the particles, direct observation and control of inflight particles and related phenomena (especially when impinging) cannot be done easily. For this reason, an experimental simulation of the particle-substrate reactions at the particle impingement was developed. This simulation is based on original flier impact experiments from laser shock acceleration of plates/foils (fliers). These were applied to the Cu-Al metallurgically-reactive system to simulate Cu cold-sprayed onto Al. The velocity of the plate was selected in the range of actual cold spray velocities. Relevant Cu-Al interaction phenomena were featured and studied as a function of flier impact conditions, i.e., primarily, shearing, plastic deformation, phase transformation (including rapid melting/solidification and formation of intermetallics). These phenomena were shown to be similar to those involved in cold spray. This was ascertained by a parallel study of cold-sprayed Cu coating of Al using SEM, TEM, EPMA, and an energy balance and diffusion calculations. In addition, this simulation can be used to feed FE modeling of cold spray particle impingement on the substrate. Preliminary results are discussed from modeling using the “RADIOSS®” code. More generally, laser shock flier impact experiments were demonstrated to result in a powerful tool capable of simulating cold spray coating-substrate interface mechanisms. Major assets rest on their high significance, reproducibility, flexibility and potential for substituting for direct laborious cold spray optimization testing.